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Background Pheochromocytomatosis is a rare but dramatic complication of pheochromocytoma surgery. In this study, we collected and analysed our experience with the surgical treatment of cases of this rare condition. Methods In total 9 patients were operated on between December 2001 and August 2022 at the Kliniken Essen-Mitte due to pheochromocytomatosis. There were 5 female and 4 male patients, mean age of 58 ± 18 (range: 22 to 86). The data was prospectively collected and retrospectively analysed. Results All patients were initially operated on due to pheochromocytoma (2 with SDHB-Syndrome and 1 with MEN-IIa-Syndrome). In 4 cases an intraoperative tumour capsule injury during the initial surgery was described. The operation due to pheochromocytomatosis was performed minimally invasive in 8 cases, 1 patient was operated on by open approach. The mean time between the primary surgery and the pheochromocytomatosis operation was 107 ± 60 months. Operation time was 246 + 119 minutes. Follow-up data were available for 8 patients (mean follow-up time 12 years). 2 patients were cured at the time of the last follow-up. 7 patients developed recurrent disease: loco-regional recurrence in 6 cases and distant metastasis in 3 cases. 4 patients with loco-regional recurrence were reoperated within 54 ± 50 months (range 10–137 months). By the follow-up, 3 patients died. Conclusion Pheochromocytomatosis is a potentially lethal complication of pheochromocytoma surgery. Even if the initial pheochomocytomatosis could be managed minimally invasive, the recurrence rate is extremely high.

123/131I-MIBG scintigraphy has shown a high specificity for imaging pheochromocytoma and paraganglioma however with low sensitivity due to low spatial resolution. 124I-MIBG PET may overcome this limitation to improve the staging of patients with (suspected) pheochromocytoma. Methods: We analyzed the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of 124I-MIBG PET in 43 consecutive patients with suspected (recurrence of) pheochromocytoma using histopathological (n = 25) and clinical validation (n = 18) as standard of truth. Furthermore, we compared 124I-MIBG PET versus contrast enhanced CT (CE-CT) per-patient and per-lesion detection rate of 124I-MIBG PET in 13 additional patients with known metastatic malignant pheochromocytoma (MMP). Results:124I-MIBG PET/CT was positive in 19/43 (44%) patients with suspected pheochromocytoma. Presence of pheochromocytoma was confirmed in 22/43 (51%). 124I-MIBG PET/CT sensitivity, specificity, PPV, NPV were 86%, 100%, 100%, 88%, respectively. 124I-MIBG PET was positive in 11/13 (85%) MMP patients. Combined 124I-MIBG PET and CE-CT detected 173 lesions, of which 166 (96%) and 118 (68%) were visible on 124I-MIBG PET and CE-CT, respectively. Discussion:124I-MIBG PET detects pheochromocytoma with high accuracy at initial staging and high detection rate at re-staging. Superior diagnostic performance aids guidance of surgical and medical management including personalized 131I-MIBG therapy.

We present the long-term cosmetic results of the video-assisted thyroidectomy (MIVAT) in comparison to the conventional operation. Forty-eight patients (four males, 44 females; mean age 47.4 ± 12.5 years) constituted the video-assisted group (VA-Group). These were compared with 48 patients (10 males, 38 females; mean age 47.4 ± 12.5 years) operated by conventional surgery (C-Group). The patients were selected from all thyroid operations performed between January 2016 and June 2017. Patient Scar Assessment Scale (PSAS) and Observer Scar Assessment Scale (OSAS) were used for the evaluation performed by an independent surgeon. Both scales contained six items scored numerically on a ten-step scale ranging from 1 (normal skin) to 10 (worst result). Moreover, photos of all scars were taken and analyzed by six team surgeons using modified OSAS. The mean follow-up time was 31.7 ± 6.4 months for the MIVAT group and 32.9 ± 4.6 months for the conventional group (p = 0.39). The mean scar length in the VA-Group was 2.6 cm vs. 3.8 cm in the C-Group (p < 0.0001). The total score of PSAS was 9.93 (6–35) for MIVAT and 9.72 (6–29) for conventional thyroidectomy (p = 0.22). The total OSAS score by the independent surgeon showed a better cosmetic outcome for conventional surgery (13.19 vs. 12.33; p = 0.01). The total OSAS score by the six team surgeons did not differ between both groups in five of six ratings; one surgeon favored MIVAT (12.2 vs. 13.6; p = 0.04). This study does not find cosmetic advantages of minimally invasive video-assisted thyroidectomy compared to conventional thyroidectomy.

Today, adrenalectomy can be performed by a variety of laparoscopic and retroperitoneoscopic approaches. Of particular importance are the lateral transperitoneal and the posterior retroperitoneoscopic access routes. Comparative studies of transperitoneal and retroperitoneal procedures still demonstrate heterogeneous results. Nevertheless, retroperitoneal access techniques seem to enable less postoperative pain and a faster recovery. Robotic procedures are gaining in popularity but the final importance cannot yet be determined. All minimally invasive techniques are considered to be so safe and reliable that open approaches are only justified in exceptional cases.In der Nebennierenchirurgie stehen heute laparoskopische und retroperitoneoskopische Operationsverfahren in zahlreichen Varianten zur Verfügung. Besondere Bedeutung haben inzwischen der laterale transperitoneal Zugang und der posteriore retroperitoneoskopische Zugang gewonnen. Die Ergebnisse vergleichender Studien zwischen transperitonealen und retroperitonealen Verfahren sind nach wie vor heterogen. Immerhin scheint der retroperitoneale Zugang eine geringere postoperative Schmerzbelastung und schnellere Rekonvaleszenz zu ermöglichen. Robotische Verfahren erfreuen sich zunehmender Beliebtheit, ihre finale Bedeutung kann heute noch nicht festgelegt werden. Alle minimal-invasiven Verfahren gelten als so sicher und zuverlässig, dass die offenen Methoden nur noch ausnahmsweise berechtigt sind.

Laryngeal ultrasound has been increasingly used for the evaluation of the vocal cords mobility after thyroid and parathyroid surgery. The sensitivity and positive predictive value of the method are reported to be higher than 80%. Nevertheless, the visualization rate in male patients remains low; therefore, ultrasound is not attractive for the perioperative workup in those patients. In the present study, we evaluate the ability to improve the visualization rate for male patients by using a gel pad as an interface between the skin and the ultrasound probe. Between December 2018 and January 2019, 92 male patients (mean age 49 years; range: 20–80 years) referred to our hospital with different thyroid pathologies received a laryngeal ultrasound without (TLUS) and subsequently with gel pad (G-TLUS). TLUS was performed by B-scan (probe 5–13 MHz, aperture 40 mm). The data were prospectively collected and statistically analyzed. The visualization rate in the TLUS group was 35% (32 out of 92 patients). The use of the gel pad could increase the rate to 78% (p 50 years) compared to younger individuals (TLUS: 25% vs. 45%, p

Contains fulltext : 245825.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Background Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. Methods Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. Results Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. Conclusion There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

Objective To screen for CLCN2 mutations in apparently sporadic cases of aldosterone-producing adenomas (APAs). Description Recently, CLCN2, encoding for the voltage-gated chloride channel protein 2 (ClC-2), was identified to be mutated in familial hyperaldosteronism II (FH II). So far, somatic mutations in CLCN2 have not been reported in sporadic cases of APAs. We screened 80 apparently sporadic APAs for mutations in CLCN2. One somatic mutation was identified at p.Gly24Asp in CLCN2. The male patient had a small adenoma in size but high aldosterone levels preoperatively. Postoperatively, the patient had normal aldosterone levels and was clinically cured. Conclusion In this study, we identified a CLCN2 mutation in a sporadic APA comprising about 1% of all APAs investigated. This mutation was complementary to mutations in other susceptibility genes for sporadic APAs and may thus be a driving mutation in APA formation.

Objective To evaluate the prevalence of low anterior resection syndrome (LARS) in patients with debulking surgery for primary advanced epithelial ovarian cancer and to identify potential risk factors for development of LARS. Methods We reviewed data on 552 consecutive patients with primary epithelial ovarian cancer (EOC), who underwent upfront or interval cytoreductive surgery including low anterior resection at two different academic institutions (Kliniken-Essen-Mitte, Germany, and Medical University of Vienna, Austria). Intestinal dysfunction was assessed by the validated LARS-questionnaire via telephone call. We performed descriptive statistics and a binary logistic regression model to evaluate risk factors for LARS. Results In total, 341 patients were eligible and 206 (60.4%) were successfully contacted and provided complete information. Major LARS was observed in 78 (37.9%) patients, minor LARS in 44 (21.4%) patients, and no LARS in 84 (40.8%) patients. The prevalence rate of major LARS was not influenced by time interval between surgery and LARS assessment, type of cytoreductive surgery, and recurrent disease at the time of assessment. In multivariate analyses, number of anastomosis was independently associated with an increased risk for presence of major LARS (OR 3.76 [1.95–7.24]). In the present cohort, 25.2% patients had more than one bowel anastomosis. Conclusions LARS in general and major LARS in particular seem to be a frequent long-term complication after debulking surgery including low anterior resection in primary advanced EOC patients. Particularly EOC patients with more than one bowel anastomosis during surgery seem to be at an increased risk for major LARS.

A positive and concordant result of at least two diagnostic modalities is generally recommended prior to focused parathyroidectomy. The aim of this study was to analyze the results of surgery and the accurateness of preoperative ultrasonography (US) as single localization modality in patients who underwent parathyroidectomy without the adjunct of intraoperative Parathormone (PTH) measurement. The cases with a preoperative US as the only localization technique, who underwent parathyroidectomy between 10/1999 and 12/2017, were selected from a prospectively maintained database. Therefore, a total number of 242 patients with a mean age of 58.6 ± 13.7 years were included in the present study. US was performed by referral endocrinologist or by the surgeon during office visits. The overall “cure rate” was 99.2% (240 out of 242 patients). In 228/242 patients (94.2%), a drop of perioperative PTH levels consistent with the definition of cure was observed on the day of surgery. In four of the remaining 14 patients, healing was confirmed by PTH level dropping into the normal range on the first postoperative day. Eight patients were cured after a reoperation was performed at our department. Postoperative complications included one case of permanent recurrent laryngeal nerve palsy (0.4%). If performed by an experienced endocrinologist and/or endocrine surgeon, a positive US could be the only preoperative localization study in patients with pHPT. Moreover, the add-value of intraoperative PTH is limited. Major advantages of US are a very high accuracy, the ease of performance (accessibility) and its cost-effectiveness compared with Sesta-MIBI scintigraphy.

Introduction: Nowadays, the standard procedures of removing benign adrenal tumors are minimally invasive surgical techniques using the laparoscopic or the retroperitoneoscopic route. In ad...

Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To date, no studies have used a genome-wide association study (GWAS) approach to search for predisposing loci for APAs. Thus, we investigated Scandinavian APA cases (n=35) and Swedish controls (n=60) in a GWAS and discovered a susceptibility locus on chromosome Xq13.3 (rs2224095, OR=7.9, 95% CI=2.8-22.4, P=1x10(-7)) in a 4-Mb region that was significantly associated with APA. Direct genotyping of sentinel SNP rs2224095 in a replication cohort of APAs (n=83) and a control group (n=740) revealed persistently strong significance (OR=6.1, 95% CI=3.5-10.6, pFunding Agencies|Linkoping University; ALF Grants (Region Ostergotland); Norwegian Health Authorities of Western Norway [F-12540]; Norwegian Cancer SocietyNorwegian Cancer Society [171752-PR-2009-0222]

Background: During resections of phaeochromocytoma release of catecholamines can lead to excessive hypertension and arrhythmia. Therefore, these procedures can be stressful to surgeons and anaesthetists. It is completely unknown, how the excessive catecholamine concentrations in phaeochromocytoma patients relate to catecholamine concentrations of physiological stress of physicians and control patients undergoing adrenalectomy because of hormone inactive tumours. We measured catecholamine concentrations, heart rate and blood pressure in patients with phaeochromocytoma, incidentaloma, a surgeon and an anaesthetist. Methods: After approval of the local ethics committee, we measured metanephrine and normetanephrine plasma concentrations in 8 patients with phaeochromocytoma, 6 control patients with incidentaloma, one surgeon and one anaesthetist at rest, after incision, after 20 and 40 minutes of surgery, and in recovery. Moreover, blood pressure and heart rate were obtained. Results: Intraoperatively significant increases of blood pressure, metanephrine and normetanephrine were found in patients and surgeon. Significant increase of normetanephrine was also found in control patients. But catecholamine concentrations in patients with phaeochromocytoma were 18 to 42 times higher than in control patients and physicians. Heart rate analysis showed no significant results. Conclusion: During phaeochromocytoma resections significant increases in catecholamine concentration and blood pressure can be found in patients and physicians. The excessive increase of catecholamine concentrations in phaeochromocytoma patients, was not always reflected by a corresponding blood pressure increase. Interestingly, although catecholamine concentrations in phaeochromocytoma patients almost normalize directly after surgery, their blood pressure remains stable without the need for pharmacological support.

Laryngeal ultrasound has been increasingly used for the evaluation of the vocal cords mobility after thyroid and parathyroid surgery. The sensitivity and positive predictive value of the method are reported to be higher than 80%. Nevertheless, the visualization rate in male patients remains low; therefore, ultrasound is not attractive for the perioperative workup in those patients. In the present study, we evaluate the ability to improve the visualization rate for male patients by using a gel pad as an interface between the skin and the ultrasound probe.Between December 2018 and January 2019, 92 male patients (mean age 49 years; range: 20-80 years) referred to our hospital with different thyroid pathologies received a laryngeal ultrasound without (TLUS) and subsequently with gel pad (G-TLUS). TLUS was performed by B-scan (probe 5-13 MHz, aperture 40 mm). The data were prospectively collected and statistically analyzed.The visualization rate in the TLUS group was 35% (32 out of 92 patients). The use of the gel pad could increase the rate to 78% (p 0.0001). For both groups, visualization rates are lower in older patients ( 50 years) compared to younger individuals (TLUS: 25% vs. 45%, p 0.05; G-TLUS: 75% vs 82%, p = 0.45).The gel pad significantly improves the vocal cord visualization rate in male patients and should be used routinely.

We present the long-term cosmetic results of the video-assisted thyroidectomy (MIVAT) in comparison to the conventional operation.Forty-eight patients (four males, 44 females; mean age 47.4 ± 12.5 years) constituted the video-assisted group (VA-Group). These were compared with 48 patients (10 males, 38 females; mean age 47.4 ± 12.5 years) operated by conventional surgery (C-Group). The patients were selected from all thyroid operations performed between January 2016 and June 2017. Patient Scar Assessment Scale (PSAS) and Observer Scar Assessment Scale (OSAS) were used for the evaluation performed by an independent surgeon. Both scales contained six items scored numerically on a ten-step scale ranging from 1 (normal skin) to 10 (worst result). Moreover, photos of all scars were taken and analyzed by six team surgeons using modified OSAS.The mean follow-up time was 31.7 ± 6.4 months for the MIVAT group and 32.9 ± 4.6 months for the conventional group (p = 0.39). The mean scar length in the VA-Group was 2.6 cm vs. 3.8 cm in the C-Group (p0.0001). The total score of PSAS was 9.93 (6-35) for MIVAT and 9.72 (6-29) for conventional thyroidectomy (p = 0.22). The total OSAS score by the independent surgeon showed a better cosmetic outcome for conventional surgery (13.19 vs. 12.33; p = 0.01). The total OSAS score by the six team surgeons did not differ between both groups in five of six ratings; one surgeon favored MIVAT (12.2 vs. 13.6; p = 0.04).This study does not find cosmetic advantages of minimally invasive video-assisted thyroidectomy compared to conventional thyroidectomy.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel–Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10–75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]). The optimal cut-off point for MA (32 HU) was calculated using the Martingale residuals method, and previously reported cut-offs for SMI were used. Logistic regression was used to determine univariate and multivariate factors associated with OS. Sarcopenia defined as SMI 0 (13.2 vs. 3.1%), comorbidity (age-adjusted Charlson Comorbidity Index [ACCI] ≥ 4; 36.8 vs. 13.3%), median body mass index (BMI; 27 vs. 24 kg/m2), International Federation of Gynecology and Obstetrics (FIGO) stage, histology (high-grade serous 95.6 vs. 84.7%), and complete resection (38.2 vs. 68.2%). MA

We evaluated the prognostic impact of the age-adjusted Charlson Comorbidity Index (ACCI) on both postoperative morbidity and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) treated at a tertiary gynecologic cancer center. Exploratory analysis of our prospectively documented tumor registry was performed. Data of all consecutive patients with stage IIIB–IV ovarian cancer who underwent primary cytoreductive surgery (PDS) from January 2000 to June 2016 were analyzed. Patients were divided into three groups, based on their ACCI: low (0–1), intermediate (2–3), and high (≥4), and postoperative surgical complications were graded according to the Clavien–Dindo classification (CDC). The Fisher’s exact test, log-rank test, and Cox regression models were used to investigate the predictive value of the ACCI on postoperative complications and OS. Overall, 793 consecutive patients were identified; 328 (41.4%) patients were categorized as low ACCI, 342 (43.1%) as intermediate ACCI, and 123 (15.5%) as high ACCI. A high ACCI was significantly associated with severe postoperative complications (CDC 3–5; odds ratio 3.27, 95% confidence interval 1.97–5.43, p

Objective To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. Methods We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. Results AL occurred in 36/800 (4.5%; 95% confidence interval [3%–6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%–9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%–13%]) than in patients with rectosigmoid resection only (6.9% [4%–10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2–3.4], p=0.01). Conclusion In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections.

Background Results of the PreOperative therapy in Esophagogastric adenocarcinoma Trial (POET) showed some benefits when including radiotherapy into the preoperative treatment. This article is reporting long-term results of this phase III study. Patients and methods Patients with locally advanced adenocarcinomas of the oesophagogastric junction (Siewert types I–III) were eligible. Randomisation was done to chemotherapy (group A) or induction chemotherapy and chemoradiotherapy (CRT; group B) followed by surgery. Results The primary end-point of the study was overall survival at 3 years. The study was closed early after 119 patients having been randomised and were eligible. Local progression-free survival after tumour resection was significantly improved by CRT (hazard ratio [HR] 0.37; 0.16–0.85, p = value 0.01) and 20 versus 12 patients were free of local tumour progression at 5 years (p = 0.03). Although the rate of postoperative in-hospital mortality was somewhat higher with CRT (10.2% versus 3.8%, p = 0.26), more patients were alive at 3 and 5 years after CRT (46.7% and 39.5%) compared with chemotherapy (26.1% and 24.4%). Thus, overall survival showed a trend in favour of preoperative CRT (HR 0.65, 95% confidence interval [CI] 0.42–1.01, p = 0.055). Conclusion Although the primary end-point overall survival of the study was not met, our long-term follow-up data suggest a benefit in local progression-free survival when radiotherapy was added to preoperative chemotherapy in patients with locally advanced adenocarcinoma of the oesophagogastric junction.

The distribution of malignant tumors is strongly related to gender due to sex-related organ and tissue differentiation. Neoplasias of the adrenal glands are relatively common and typically benign. Mainly based on our recently published contributions, we analyzed the influence of gender on type of tumors, complexity of surgery, and long-term outcome. Cortisol-secreting adrenal tumors are more often diagnosed in female patients, while the incidence of Conn’s syndrome and pheochromocytoma is similar between male and female patients. Adrenalectomy is more difficult in male patients because of longer operating time and higher blood loss. The probability of cure in male patients with Conn’s syndrome is significantly lower. Gender does not influence long-term results in adrenal hypercortisolism and pheochromocytomas.

In recent years, educational theory and empirically oriented educational research have been viewed in contrary light. Growing interest in evidence-based expertise in education and the increase in assessment of competences reinforced this debate. The aim of this contribution is to question this contradiction, and to consider possibilities of constructive collaboration between educational theory and empirical research in assessment of competences. The aim is to stimulate new formats of assessment. We discuss education as a holistic transformation and a social process. According to this understanding, we identify communication competences as an educational aim and discuss opportunities of its training and assessment. We suggest role-plays as an adequate method to develop a competence-based instrument. Ten specific role-plays were developed, which were applied by N = 515 students. The results support role-plays as an effective and reliable assessment of communication competences. Nevertheless, further analyses are necessary to detect and explain various effects and gains in competences. The combination of empirical educational research and educational theory seems to be promising, and we hope to discover further conceptual impacts by bringing both sides together.

The morphological differentiation between benign and malignant adrenocortical tumors is an ongoing problem in diagnostic pathology. In recent decades the complex scoring systems have been widely used to calculate the probability of malignancy in adrenocortical tumors on the basis of a variety of histomorphological parameters. We herewith present a substantially simplified method to diagnose adrenocortical carcinoma by a single histomorphological parameter on a consecutive series of more than 800 adrenocortical tumors. Between January 2000 and May 2019, altogether 2305 adrenalectomies for of all types of diseases were removed, approximately 98% by minimally invasive approaches. After exclusion of pheochromocytomas, adrenal ganglioneuromas, adrenal metastases, Cushing’s disease related specimens, and Conn’s adenomas, the present series finally consisted of 837 adrenocortical tumors. All tumors were analyzed by experienced pathologists of a single institution using standard histopathological methods (Hematoxylin-Eosin and Ki67 stained sections). Clinical and histopathologic data were prospectively collected and retrospectively analyzed. Clinically, 385 patients had 420 functioning tumors (FT), and 417 had non-functioning adrenal tumors (NFT). The mean size of FT was 3.8 ± 1.4 cm (range 0.5–16 cm) and for NFT 4.5 ± 1.6 cm (range 1.5–18 cm). Histomorphologically, 32 adrenal tumors were classified as adrenocortical carcinoma (ACC; 3.8%). In all 32 cases (tumor size 9.1 ± 4.0 cm, range 3–18 cm), confluenting tumor necrosis could be demonstrated. The remaining 805 tumors (control group) completely lacked this highly reproducible single morphological feature. Ki67 levels above 10% were found in 31 of 32 ACCs and never in adrenocortical adenomas (ACA). With a mean follow-up of 8.2 years, 24 out of 32 patients primarily diagnosed as ACC developed distant metastases (75.0%), whereas all patients in the control group remained free of local or distant recurrence. We conclude that a single morphological parameter (confluenting tumor necrosis) is sufficient to predict a poor clinical course in adrenocortical tumors. The histomorphological diagnosis of this parameter is straightforward and highly reproducible.

A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function.Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer-assisted quantitative fluorescence imaging, contrast-enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy.Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments.In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands. Surgical relevance Preservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown. New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast-enhanced intraoperative CT showed congruent results in evaluation of perfusion. Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.Un abordaje quirúrgico que preserve la función del tejido suprarrenal permite lograr la curación bioquímica, a la vez que evita la necesidad de tratamiento sustitutivo con corticoides de por vida. El objetivo de este estudio experimental fue evaluar el impacto de las técnicas de imagen intraoperatorias en la suprarrenalectomía parcial (partial adrenalectomy, AE) bilateral sobre la perfusión y función del remanente glandular. MÉTODOS: Cinco cerdos fueron sometidos a una división bilateral central de la glándula suprarrenal por retroperitoneoscopia posterior (n = 9, 1 sin dividir). Durante la intervención, la evaluación de la perfusión incluyó la fluorescencia con cuantificación asistida por ordenador (Realidad Aumentada basada en la Fluorescencia, FLuorescence-based Enhanced Reality, FLER), tomografía computarizada (computed tomography, CT), endomicroscopia con laser confocal (confocal laser endomicroscopy, CLE) y un muestreo local de lactato. El análisis de la pieza quirúrgica tras completar la AE (n = 10) incluyó actividad mitocondrial y microscopia electrónica.La evolución de la intensidad de la señal de fluorescencia a lo largo del tiempo (ΔI/s) fue significativamente más baja en el segmento craneal de cada una de las glándulas (0,052 ± 0,057 craneal versus 0,133 ± 0,057 caudal, P = 0,02). De forma concordante, la CT intraoperatoria en la fase portal demostró una captación de contraste significativamente más baja en los segmentos craneales (P = 0,03). En la CLE, el contraste de fluoresceína se observó en todos los segmentos caudales, pero solo en el 44% de los segmentos craneales (P = 0,04). Los hallazgos obtenidos en las pruebas de imagen favorables a la perfusión caudal fueron congruentes con niveles significativamente más bajos de lactato capilar a nivel local (11,58 ± 6,53 mmol/L craneal versus 5,66 ± 5,79 mmol/L caudal, P = 0,008). A nivel craneal, la microscopia electrónica mostró más células necróticas (P = 0,03). La actividad mitocondrial (tasas de respiración, especies reactivas de oxígeno y producción de H

We present a case of ectopic thyroid tissue in the adrenal gland and discuss the findings with regard to the literature. Ectopic thyroid tissue below the diaphragm is rare and the mechanism of development is poorly understood. From a differential diagnostic point of view, it is important to exclude metastatic spread from a thyroid primary.

Introduction/Background The low anterior resection syndrome (LARS) is a long-term complication observed in patients after low anterior resection (LAR). LARS comprises a collection of intestinal dysfunction symptoms, such as diarrhea, fecal incontinence, increased frequencies of defecation, fecal urgency or incomplete emptying. Diagnosis of LARS is based on the LARS score, a validated questionnaire consisting of five questions and classifies symptoms as ‘no LARS’, ‘minor LARS’ or ‘major LARS’. Evidence for LARS is exclusively based on studies for rectal cancer. The aim of the present study was to evaluate the prevalence of LARS in patients with debulking surgery for epithelial ovarian cancer (EOC) and to identify potential risk factors for development of LARS. Methodology We reviewed data on 552 consecutive patients with EOC, who underwent upfront or interval cytoreductive surgery including LAR at two academic institutions. Intestinal dysfunction was assessed by the LARS-questionnaire via telephone call. Results In total, 341 patients were eligible and 206 (60.4%) were successfully contacted and provided complete information. Major LARS was observed in 78 (37.9%) patients, minor LARS in 44 (21.4%) patients, and no LARS in 84 (40.8%) patients. The prevalence rate of major LARS was not influenced by time interval between surgery. In multivariate analyses, number of anastomosis was independently associated with an increased risk for presence of major LARS (OR 3.76 [1.95–7.24]). Conclusion LARS is a frequent long-term complication after debulking surgery including LAR in EOC patients. Patients with more than one bowel anastomoses seem to be at an increased risk for major LARS. Disclosure MK has nothing to disclose. CG received honoraria from AstraZeneca, Celgene, MSD, PharmaMar, Roche, Tesaro, Vifor Pharma; Amgen, AstraZeneca, MSD, PharmaMar, Roche, Tesaro outside of the submitted work. BA received honoraria from Roche, Amgen, Astra Zeneca, Tesaro, Clovis, Celgene, PharmaMar, outside the submitted work. SS has nothing to disclose. SR received honoraria from Medtronic, Takeda outside of the submitted work. PA has nothing to disclose. SP has nothing to disclose. MW has nothing to disclose. FH has nothing to disclose. AS received honoraria from Takeda, outside the submitted work. FH received honoraria from Roche, AstraZeneca, Clovis, Tesaro, PharmaMar, outside the submitted work. AR received honoraria from AstraZeneca, Celgene, MSD, PharmaMar, Roche, Tesaro, Vifor Pharma; Amgen, AstraZeneca, MSD, PharmaMar, Roche, Tesaro, outside of the submitted work. SP received honoraria from AstraZeneca, Celgene, MSD, PharmaMar, Roche, Tesaro, Vifor Pharma; Amgen, AstraZeneca, MSD, PharmaMar, Roche, Tesaro, outside of the submitted work. PHreceived honoraria from Astra Zeneca, Roche, Tesaro, Sotio, Stryker, ZaiLab, MSD, Lilly, Clovis, Immunogen, outside the submitted work. AdB received honoraria from Roche, Clovis, Astra Zeneca, Tesaro, Pfizer, Pharmar, Biocad, Genmab, outside of the submitted work.

The posterior retroperitoneoscopic adrenal access represents a challenge in orientation and working space creation. The aim of this experimental acute study was to evaluate the impact of computer-assisted quantitative fluorescence imaging on adrenal gland identification and assessment of intraoperative remnant perfusion for adrenal resection in the posterior retroperitoneoscopic approach. Six pigs underwent simultaneous (n = 5) or sequential (n = 1) bilateral posterior retroperitoneoscopic adrenalectomy (n = 12). Fluorescence imaging was obtained via intravenous administration of 3 mL of Indocyanine Green (ICG) and by switching the camera systems to near-infrared mode (D-LIGHT P, KARL STORZ; Germany). Fluorescence-based visualization of adrenal glands before vascular division (n = 4), after the main vascular pedicle ligation (negative control, n = 1) or after adrenal resection (n = 7), was followed by completion adrenalectomy. The fluorescence signal intensity dynamics were recorded and analyzed using proprietary software. For each pixel, the slope of fluorescence signal intensity evolution over time was translated into a color-coded perfusion cartography, which was superimposed onto real-time images obtained with the corresponding left and right camera systems. Quantitative fluorescence signal analysis in the regions of interest (ROIs) served to assess adrenal remnant perfusion in divided adrenal glands. In the retroperitoneum, the vascular anatomy was illuminated in fluorescence imaging first. The adrenal glands were promptly highlighted after primary intravenous ICG administration (n = 9) or showed a fluorescence signal intensity increase upon reinjection (n = 3). Quantitative fluorescence analysis showed a statistically significant difference between perfused and ischemic segments in divided glands (p = 0.0156). Fluorescence imaging provides real-time guidance during minimally invasive adrenal surgery. Prior to dissection, it allows to easily discriminate the adrenal gland from surrounding retroperitoneal structures. After adrenal gland division, ICG injection associated with a computer-assisted quantitative analysis helps to distinguish between well-perfused and ischemic segments. Further studies are underway to establish the correlation between remnant perfusion and viability.

Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

The treatment of hypercortisolism for patients with bilateral adrenal disease (BAD) is controversial. Bilateral total adrenalectomy results in permanent hypocortisolaemia requiring lifelong steroid replacement. A more conservative surgical approach, with less than bilateral total adrenalectomy (leaving functional adrenal tissue either unilaterally or bilaterally), represents an alternative option; however, long-term outcome or recurrence data are limited. We report our experience with the surgical management of hypercortisolism caused by BAD. Between 2004 and 2016, 42 patients (12 male, 30 female; mean age 58 ± 10 years) with clinical or subclinical Cushing’s syndrome (CS/sCS) caused by BAD underwent adrenal surgery via the posterior retroperitoneoscopic approach. Adrenal surgery was defined as “adrenalectomy” when total gland excision was performed or “resection” when a partial or subtotal adrenal resection was performed. Clinical, radiological and biochemical parameters were evaluated preoperatively and postoperatively. Seventy adrenal operations performed in total included unilateral resection (n = 3), unilateral adrenalectomy (n = 15), bilateral resection (n = 9), adrenalectomy and contralateral resection (n = 14) and bilateral total adrenalectomy (n = 3). Median operating time was 47.5 min (30–150) with no difference between unilateral and bilateral (synchronous included) procedures (p = 0.15). Mortality was zero. Clavien–Dindo grade of postoperative complications was I (n = 5) and IV (n = 3). All but one patient with CS and 17/31 patients with sCS received postoperative steroid supplementation for a median duration of 20 (1.5–129) months. After median follow-up of 40 months (3–129), the remission rate was 92%; 11 patients required ongoing steroid supplementation. There were three biochemical recurrences (two underwent contralateral resection); two patients with new/progressive radiological nodularity are biochemically eucortisolaemic. A significant reduction in BMI (p = 0.01) and antihypertensive requirements (p = 0.04) was observed postoperatively. A surgical approach which facilitates the conservation of functional adrenal tissue represents a suitable strategy for hypercortisolism caused by BAD. This approach avoids the necessity for lifelong steroid replacement in the majority of cases with low rates of adrenal insufficiency and recurrence.

The aim of the work was to investigate the effect of early thyroidectomy on the course of active Graves’ orbitopathy (GO) in patients with low probability of remission [high TSH receptor antibody (TRAb) serum levels, severe GO] compared to that of continued therapy with antithyroid drugs. Two cohorts were evaluated retrospectively (total n=92 patients with active GO, CAS≥4). Forty-six patients underwent early thyroidectomy (Tx-group) 6±2 months after initiation of antithyroid drug (ATD) therapy, while ATD was continued for another 6±2 months in the ATD-group (n=46). These controls were consecutively chosen from a database and matched to the Tx-group. GO was evaluated (activity, severity, TRAb) at baseline and at 6 month follow-up. At baseline, both cohorts were virtually identical as to disease severity, activity and duration, as well as prior anti-inflammatory treatment, age, gender, and smoking behavior. At 6 month follow-up, NOSPECS severity score was significantly decreased within each group, but did not differ between both groups. However, significantly more patients of the Tx-group presented with inactive GO (89.1 vs. 67.4%, * p=0.02), and mean CAS score was significantly lower in Tx-group (2.1) than in ADT-group (2.8; * p=0.02) at the end of follow-up. TRAb levels declined in both groups (Tx-group: from 18.6 to 5.2 vs. ATD-group: 12.8–3.2 IU/l, p 0 =0.07, p 6months =0.32). Residual GO activity was lower in Tx-group, associated with a higher rate of inactivation of GO. This allows an earlier initiation of ophthalmosurgical rehabilitation in patients with severe GO, which may positively influence quality of life of the patients.

Background: Minimally invasive liver surgery has gained increasing popularity over the past decade. Nevertheless, laparoscopic treatment of lesions located in the posterior–superior locati...

Retroperitoneal paragangliomas are rare tumors with the characteristics of adrenal pheochromocytomas. They may occur sporadically or in conjunction with hereditary syndromes. Diagnostic methods in paragangliomas include testing of catecholamine secretion and imaging procedures. The first choice treatment is surgical removal, which in the author's opinion is preferably by minimally invasive approaches. Infrarenal paragangliomas should be excised using a laparoscopic transabdominal procedure. For suprarenal tumors the retroperitoneoscopic approach should be used.

Retroperitoneal paragangliomas are rare tumors with the characteristics of adrenal pheochromocytomas. They may occur sporadically or in conjunction with hereditary syndromes. Diagnostic methods in paragangliomas include testing of catecholamine secretion and imaging procedures. The first choice treatment is surgical removal, which in the author's opinion is preferably by minimally invasive approaches. Infrarenal paragangliomas should be excised using a laparoscopic transabdominal procedure. For suprarenal tumors the retroperitoneoscopic approach should be used.

Direct flexible laryngoscopy (DFL) is the golden standard to evaluate the vocal cord (VC) function in thyroid and parathyroid surgery pre- and postoperatively. Transcutaneous laryngeal ultrasonography (TLUS) could represent an alternative to the DFL and has been evaluated in the present study comparing the results of both methods performed at two referral centers for endocrine pathologies. In the setting of a retrospective study, 668 patients (560 female, 118 male; mean age 50.3 ± 14.2) were included from two tertiary referral centers of endocrine surgery. In all patients, TLUS was performed pre- and postoperatively prior to transnasal DFL, which served as a golden standard. TLUS was performed by B-scan (probe 5–13 MHz, aperture 40 mm). Preoperative visualization of the vocal cords by TLUS was possible in 526 patients (78.7%). Due to the frequent thyroid cartilage calcification (TCC) in male patients, a significant difference in the visualization rate was found between female and male (88.7% vs. 26.8%) [p

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits

Objective The aim of this trial was to evaluate the effects of yoga on health-related quality of life in patients with colorectal cancer. Methods Patients with non-metastatic colorectal cancer were randomly assigned to a 10-week yoga intervention (90 min once weekly) or a waitlist control group. Primary outcome measure was disease-specific quality of life (Functional Assessment of Cancer Therapy – Colorectal [FACT-C]) at week 10. Secondary outcome measures included FACT-C subscales: spiritual well-being (FACT – Spirituality); fatigue (FACT – Fatigue); sleep disturbances (Pittsburgh Sleep Quality Inventory); depression and anxiety (Hospital Anxiety and Depression Scale); body awareness (Scale of Body Connection); and body-efficacy expectations (Body-Efficacy Expectations Scale). Outcomes were assessed at week 10 and week 22 after randomization. Results Fifty-four patients (mean age 68.3 ± 9.7 years) were randomized to yoga (n = 27; attrition rate 22.2%) and control group (n = 27; attrition rate 18.5%). Patients in the yoga group attended a mean of 5.3 ± 4.0 yoga classes. No significant group differences for the FACT-C total score were found. Group differences were found for emotional well-being at week 22 (∆ = 1.59; 95% CI = 0.27,2.90; p = 0.019), sleep disturbances at week 22 (∆ = −1.08; 95% CI = −2.13, −0.03; p = 0.043), anxiety at week 10 (∆ = −1.14; 95% CI = −2.20, −0.09; p = 0.043), and depression at week 10 (∆ = −1.34; 95% CI = −2.61, −0.8; p = 0.038). No serious adverse events occurred in the yoga group, while liver metastases were diagnosed in one patient in the control group. Conclusion This randomized trial found no effects of yoga on health-related quality of life in patients with colorectal cancer. Given the high attrition rate and low intervention adherence, no definite conclusions can be drawn from this trial. Copyright © 2015 John Wiley & Sons, Ltd.

Pheochromocytomas (PH) and paragangliomas (PGL) are rare tumours in children accounting for about 1% of the paediatric hypertension. While minimally invasive surgical techniques are well established in adult patients with PH, the experience in children is extremely limited. To the best of our knowledge, we herewith present the largest series of young patients operated on chromaffin tumours by minimally invasive access. In the setting of a prospective study (1/2001–12/2016), 42 consecutive children and adolescents (33 m, 9 f) were operated on. Thirty-seven patients (88%) suffered from inherited diseases. Twenty-six patients had PH, 11 presented retroperitoneal PGL, and five patients suffered from both. Altogether, 70 tumours (mean size 2.7 cm) were removed (45 PH, 25 PGL). All operations were performed by a minimally invasive access (retroperitoneoscopic, laparoscopic, extraperitoneal). Partial adrenalectomy was the preferred procedure for PH (31 out of 39 patients). Twenty patients received α-receptor blockade preoperatively. One patient died after induction of anaesthesia due to cardiac arrest. All other complications were minor. Conversion to open surgery was necessary in two cases with PGL. Median operating time for unilateral PH was 55 min, in bilateral cases 125, 143 min in PGs, and 180 min in combined cases. Median blood loss was 20 ml (range 0–1000). Blood transfusion was necessary in two cases. Intraoperative, systolic peak pressure was 170 ± 39 mmHg with α-receptor blockade and 191 ± 33 mmHg without α-receptor blockade (p = 0.41). The median post-operative hospital stay was 3 days. After a mean follow-up of 8.5 years, two patients presented ipsilateral recurrence (after partial adrenalectomy). All patients with bilateral PH (n = 13) are steroid independent post-operatively. PH and PGL in children and adolescents should preferably be removed by minimally invasive surgery. Partial adrenalectomy provides long-term steroid independence in bilateral PH and a low rate of (ipsilateral) recurrence. α-Receptor blockade may not be necessary in these patients.

WOS: 000439200100008, PubMed ID: 29794110, Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.

Background: Adrenalectomy is standard of care for phaeochromocytomas, but for bilateral phaeochromocytoma, the recommendations are inconsistent. However, large studies systematically investigating long-term outcomes for total adrenalectomies compared to those for patients with adrenal-sparing operations are lacking. Methods: A multi-center consortium-based registry was established to study clinical, genetic and surgical data in 623 patients with bilateral phaeochromocytomas. Findings: Of 623 patients, median age at diagnosis was 30 (range 3-79) years and 48% were female. Synchronous bilateral phaeochromocytomas were diagnosed in 396 patients and metachronousphaeochromocytomas in 227 (36%); interval to second operations were up to 40 (median 6) years. In 96% of tested patients germline mutations were detected in the genes RET (56%), VHL (34%), and others (10%). Of 849 operations, 385 (45%) surgeries in 326 patients were planned as adrenal-sparing which was successful in 251. 372 patients became steroid-dependent. Follow-up was up to 53 (median 11) years. Adrenal crises developed in 67 patients (18%) during follow-up, and 49 (13%) had manifestations of iatrogenic Cushing syndrome. Of the steroid-independent patients, 34 (14%) had developed another phaeochromocytoma within the remnant adrenal after up to 27, median 8 years, all treated with removal of the new phaeochromocytoma. Overall survival was mainly influenced by non-phaeochromocytoma comorbidities, whereas only 1% died of metastatic phaeochromocytoma. Cortical-sparing operations did not affect survival. Interpretation: Cortical-sparing operations avert lifelong steroid-dependency without affecting survival. Preoperative genetic testing is recommended even in unilateral phaeochromocytoma presentations to identify patients at heritable risk, to guide surgical approach, and inform for gene-specific extra-adrenal morbidities. Funding Statement: Supported in part by the grant AZV 16-32665A to Sarka Dvorakova and Petr Vlcek, and the Blank Foundation to Charis Eng. Declaration of Interests: None of the authors have relevant conflicts of interest. Ethics Approval Statement: The institutional review boards for human subjects’ protection or ethical committees of all participating centers approved this study. Patients provided written informed consent according to the protocols of respective institutional review boards. In The Netherlands data were collected anonymously, and no further Institutional Review Board approval is required.